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1.
J Phys Chem Lett ; : 7028-7035, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949686

ABSTRACT

Traditional electron counting rules, like the Jellium model, have long been successfully utilized in designing superhalogens by modifying clusters to have one electron less than a filled electronic shell. However, this shell-filling approach, which involves altering the intrinsic properties of the clusters, can be complex and challenging to control, especially in experiments. In this letter, we theoretically establish that the oriented external electric field (OEEF) can substantially enhance the electron affinity (EA) of diverse aluminum-based metal clusters with varying valence electron configurations, leading to the creation of superhalogen species without altering their shell arrangements. This OEEF approach offers a noninvasive alternative to traditional superatom design strategies, as it does not disrupt the clusters' geometrical structures and superatomic states. These findings contribute a vital piece to the puzzle of constructing superalkalis and superhalogens, extending beyond conventional shell-filling strategies and potentially expanding the range of applications for functional clusters.

2.
J Hazard Mater ; 476: 135050, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38954852

ABSTRACT

Spent lithium-ion batteries (LIBs) have emerged as a major source of waste due to their low recovery rate. The physical disposal of spent LIBs can lead to the leaching of their contents into the surrounding environment. While it is widely agreed that hazardous substances such as nickel and cobalt in the leachate can pose a threat to the environment and human health, the overall composition and toxicity of LIB leachate remain unclear. In this study, a chemical analysis of leachate from spent LIBs was conducted to identify its primary constituents. The ecotoxicological parameters of the model organism, rotifer Brachionus asplanchnoidis, were assessed to elucidate the toxicity of the LIB leachate. Subsequent experiments elucidated the impacts of the LIB leachate and its representative components on the malondialdehyde (MDA) level, antioxidant capacity, and enzyme activity of B. asplanchnoidis. The results indicate that both the LIB leachate and its components are harmful to individual rotifers due to the adverse effects of stress-induced disturbances in biochemical indicators, posing a threat to population development. The intensified poisoning phenomenon under combined stress suggests the presence of complex synergistic effects among the components of LIB leachate. Due to the likely environmental and biological hazards, LIBs should be strictly managed after disposal. Additionally, more economical and eco-friendly recycling and treatment technologies need to be developed and commercialized.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 559-566, 2024 Jun 15.
Article in Chinese | MEDLINE | ID: mdl-38926371

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of subcutaneous immunotherapy (SCIT) using dust mites in children with allergic asthma. METHODS: In a prospective randomized controlled study, 98 children with dust mite-induced allergic asthma were randomly divided into a control group (n=49) and an SCIT group (n=49). The control group received inhaled corticosteroid treatment, while the SCIT group additionally received a standardized three-year SCIT regimen. The two groups were compared based on peripheral blood eosinophil percentage, visual analogue score (VAS), total medication score, Asthma Control Test/Childhood Asthma Control Test scores, fractional exhaled nitric oxide (FeNO), and lung function before treatment, and at 6 months, 1 year, 2 years, and 3 years after treatment. Adverse reactions were recorded post-injection to evaluate the safety of SCIT. RESULTS: Compared with pre-treatment levels, the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils, VAS, total medication score, and FeNO, while lung function significantly improved, and asthma control levels were better 3 years after treatment (P<0.05). Compared with the control group, the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment (P<0.05). A total of 2 744 injections were administered, resulting in 157 cases (5.72%) of local adverse reactions and 4 cases (0.15%) of systemic adverse reactions, with no severe systemic adverse events. CONCLUSIONS: SCIT is an effective and safe treatment for allergic asthma in children.


Subject(s)
Asthma , Pyroglyphidae , Humans , Asthma/therapy , Asthma/immunology , Male , Child , Female , Animals , Prospective Studies , Injections, Subcutaneous , Pyroglyphidae/immunology , Child, Preschool , Desensitization, Immunologic/methods , Desensitization, Immunologic/adverse effects , Adolescent
5.
Magn Reson Chem ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867454

ABSTRACT

Copper(II) chloride anionic coordination complexes with different imidazole-derived ligands due to the potential cytotoxic activity play the important role in protein. By investigating the experimental electron paramagnetic resonance (EPR) and ultraviolet-visible (UV-vis) spectra of [CuCl(C6H10N2)4]Cl, [CuCl(C6H10N2)4]Cl, [CuCl2(C4H6N2)4], and [Cu2Cl2(C5H8N2)6]Cl2·2H2O, the local structure of the corresponding Cu2+ centers and the role of different ligands are obtained. Based on the well-agreed EPR parameters and the d-d transitions (10Dq), the four Cu2+ centers show tetragonal and orthorhombic distortion, corresponding to the different anisotropies of EPR signals. In addition, the general rules of governing the impact of methanol in imidazolylalkyl derivatives are also discussed, especially the influence on the local environment (symmetry, distortion, covalency, and crystal field) of above four copper(II) chloride anionic coordination complexes. Therefore, the obtained results in this study will be beneficial to provide a theoretical basis for the experimental design of desired copper-containing imidazolyl alkyl derivatives.

6.
BMC Cancer ; 24(1): 671, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824581

ABSTRACT

BACKGROUND: The role of novel circular RNAs (circRNAs) in colorectal cancer (CRC) remains to be determined. This study aimed to identify a novel circRNA involved in CRC pathogenesis, assess its diagnostic value, and construct a regulatory network. METHODS: Differential expression analysis was conducted using circRNA datasets to screen for differentially expressed circRNAs. The expression of selected circRNAs was validated in external datasets and clinical samples. Diagnostic value of plasma circRNA levels in CRC was assessed. A competing endogenous RNA (ceRNA) network was constructed for the circRNA using TCGA dataset. RESULTS: Analysis of datasets revealed that hsa_circ_101303 was significantly overexpressed in CRC tissues compared to normal tissues. The upregulation of hsa_circ_101303 in CRC tissues was further confirmed through the GSE138589 dataset and clinical samples. High expression of hsa_circ_101303 was associated with advanced N stage, M stage, and tumor stage in CRC. Plasma levels of hsa_circ_101303 were markedly elevated in CRC patients and exhibited moderate diagnostic ability for CRC (AUC = 0.738). The host gene of hsa_circ_101303 was also found to be related to the TNM stage of CRC. Nine miRNAs were identified as target miRNAs for hsa_circ_101303, and 27 genes were identified as targets of these miRNAs. Subsequently, a ceRNA network for hsa_circ_101303 was constructed to illustrate the interactions between the nine miRNAs and 27 genes. CONCLUSIONS: The study identifies hsa_circ_101303 as a highly expressed circRNA in CRC, which is associated with the progression of the disease. Plasma levels of hsa_circ_101303 show promising diagnostic potential for CRC. The ceRNA network for hsa_circ_101303 provides valuable insights into the regulatory mechanisms underlying CRC.


Subject(s)
Biomarkers, Tumor , Colorectal Neoplasms , Gene Expression Regulation, Neoplastic , Gene Regulatory Networks , MicroRNAs , RNA, Circular , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , RNA, Circular/genetics , RNA, Circular/blood , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Male , Female , MicroRNAs/genetics , MicroRNAs/blood , Middle Aged , Gene Expression Profiling , Neoplasm Staging
7.
Article in English | MEDLINE | ID: mdl-38875163

ABSTRACT

AIM: To synthesise the qualitative evidence on dyadic relationships between informal caregivers (ICs) and older adults with chronic heart failure (HF). METHODS AND RESULTS: A systematic review and meta-synthesis were conducted. Eight databases were searched for English peer-reviewed studies and grey literature published from inception to 27 February 2024. Qualitative and mixed-method studies involving older adults ≥ 55 years old with chronic HF and discussing patient-caregiver relationships in community settings were included. Data were synthesised using Sandelowski and Barroso's 2-step framework. A meta-summary was developed using thematic analysis, and findings were synthesised using the Theory of Dyadic Illness Management. Twenty-four studies from 2008 to 2024 were included (n = 580 participants). The meta-summary consisted of four themes and nine subthemes: (1) Characteristics of dyad relationships, (2) How both parts of the dyad care for each other, (3) Chronic HF and dyad relationships, (4) Knowledge of managing chronic HF. These were reorganised into the meta-synthesis: dyadic appraisal, dyadic management behaviours, dyadic health, contextual factors affecting dyadic relationships and management behaviours, and illness management as a dyadic phenomenon. CONCLUSION: Investigating relationship dynamics and their impact on dyads and chronic HF self-care is vital. Where possible, healthcare providers should prioritise dyadic care when caregivers are involved and deliver individualised care to improve patient and caregiver outcomes. Assessing and optimising dyadic relations, addressing individual perceptions and needs as part of clinical care, and before implementing self-care interventions in research may help ensure that self-care is appropriately tailored and would not be hindered by relationship conflicts.

8.
Ying Yong Sheng Tai Xue Bao ; 35(4): 1112-1122, 2024 Apr 18.
Article in Chinese | MEDLINE | ID: mdl-38884246

ABSTRACT

River water quality is influenced by natural processes and human activities. Multi-scale landscape patterns can affect river water quality by altering the generation and transport processes of pollutants at different spatial scales. Taking Taizi River Basin in Northeast China as an example, we analyzed the relationship between landscape patterns and non-point source pollution in rivers based on water quality monitoring data and land use data by using correlation analysis and redundancy analysis methods. We aimed to determine the key spatial scales for the responses of landscape patterns to non-point source pollution and identify the key landscape indices influencing river non-point source pollution. The results showed that water quality of Taizi River Basin had seasonal differences, with better water quality during the flood season than non-flood season. Spatially, total nitrogen (TN) and total phosphorus (TP) were higher at the confluence points of tributaries and downstream areas. The impact of landscape patterns on non-point source pollution was stronger during the non-flood season than the flood season, while the influence on TN was stronger than on TP. At the spatial scale of within 500 m buffer zone during the flood season and at the sub-watershed scale during the non-flood season, landscape patterns showed the highest explanatory power for the variations of TN and TP. At the type level, built-up land, cropland, and bare land were positively correlated with TN and TP, while forest was negatively correlated with TN and TP, which were the key types influencing non-point source pollution. At the landscape level, patch density, percentage of like adjacencies, and contagion index were key indicators affecting watershed water quality. Lower patch density was associated with better connectivity and aggregation of "sink" landscapes, leading to better purification effects on TN, but more pronounced retention effects on TP. Conversely, higher landscape diversity and denser pattern of multiple types would cause the deterioration of water quality. Our results suggested that rational allocation of landscape types within the watershed and riparian buffer zones, appropriately enriching landscape diversity, and optimizing landscape aggregation and connectivity would be effective measures for improving water quality and achieving sustainable ecological management.


Subject(s)
Environmental Monitoring , Phosphorus , Rivers , Water Pollutants, Chemical , China , Rivers/chemistry , Environmental Monitoring/methods , Water Pollutants, Chemical/analysis , Phosphorus/analysis , Ecosystem , Nitrogen/analysis , Non-Point Source Pollution/analysis , Non-Point Source Pollution/prevention & control , Water Quality , Spatial Analysis
9.
Neuropharmacology ; 257: 110034, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878858

ABSTRACT

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

10.
J Phys Chem A ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38917472

ABSTRACT

The identification of the non-noble metal constituted TaO cluster as a potential analogue to the noble metal Au is significant for the development of tailored materials. It leverages the superatom concept to engineer properties with precision. However, the impact of incrementally integrating TaO units on the electronic configurations and properties within larger TaO-based clusters remains to be elucidated. By employing the density functional theory calculations, the global minima and low-lying isomers of the TanOn (n = 2-5) clusters were determined, and their structural evolution was disclosed. In the cluster series, Ta5O5 was found to possess the highest electron affinity (EA) with a value of 2.14 eV, based on which a dual external field (DEF) strategy was applied to regulate the electronic property of the cluster. Initially, the electron-withdrawing CO ligand was affixed to Ta5O5, followed by the application of an oriented external electric field (OEEF). The CO ligation was found to be able to enhance the Ta5O5 cluster's electron capture capability by adjusting its electron energy levels, with the EA of Ta5O5(CO)4 peaking at 2.58 eV. Subsequently, the introduction of OEEF further elevated the EA of the CO-ligated cluster. Notably, OEEF, when applied along the +x axis, was observed to sharply increase the EA to 3.26 eV, meeting the criteria for superhalogens. The enhancement of EA in response to OEEF intensity can be quantified as a functional relationship. This finding highlights the advantage of OEEF over conventional methods, demonstrating its capacity for precise and continuous modulation of cluster EAs. Consequently, this research has adeptly transformed tantalum oxide clusters into superhalogen structures, underscoring the effectiveness of the DEF strategy in augmenting cluster EAs and its promise as a viable tool for the creation of superhalogens.

11.
PLoS One ; 19(6): e0305594, 2024.
Article in English | MEDLINE | ID: mdl-38885267

ABSTRACT

Urban agglomerations (UAs), which serve as pivotal hubs for economic and innovative convergence, play a crucial role in enhancing internal circulation and strengthening external linkages. This study utilizes the China city-level multi-regional input-output tables, incorporating the Dagum Gini coefficient and kernel density estimation methods, to perform a thorough quantitative analysis. Disparities within the national and global value chains ("dual value chains") of Chinese UAs from 2012 to 2017 were assessed. Additionally, the logarithmic mean Divisia index (LMDI) method was applied to disaggregate the drivers of both national and global intermediate inputs (NII and GII). The study's key findings include the following: (1) The national value chain (NVC) within UAs exhibits robust growth, contrasting with the decline in the global value chain (GVC). (2) The inter-UA disparity contribution rate significantly surpasses the combined rates of intra-UA contribution and super-variation density. (3) Distinct evolutionary peak trends are discerned among various UAs within the "dual value chains", highlighting diverse spatial polarization characteristics and expansiveness. (4) The growth of the NVC has transitioned from a negative to a positive impact on NII, while the decline in GVC has substantially counteracted GII growth. Economic and demographic factors notably drive positive improvements in both NII and GII, whereas the efficiency of outflows presents a negative driving effect. Based on these findings, this study offers strategic recommendations to facilitate the effective integration of UAs into the new development paradigm, thereby providing a scientific basis for related decision-making processes.


Subject(s)
Cities , China , Humans , Urbanization/trends , Economic Development/trends
12.
Foods ; 13(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38890863

ABSTRACT

The adsorption characteristics of ß-glucooligosaccharides on activated carbon and the purification were systematically investigated. The maximum adsorption capacity of activated carbon reached 0.419 g/g in the optimal conditions. The adsorption behavior was described to be monolayer, spontaneous, and exothermic based on several models' fitting results. Five fractions with different degrees of polymerization (DPs) and structures of ß-glucooligosaccharides were obtained by gradient ethanol elution. 10E mainly contained disaccharides with dp2a (G1→6G) and dp2b (G1→3G). 20E possessed trisaccharides with dp3a (G1→6G1→3G) and dp3b (G1→3G1→3G). 30E mainly consisted of dp3a and dp4a (G1→3G1→3(G1→6)G), dp4b (G1→6G1→3G1→3G), and dp4c (G1→3G1→3G1→3G). In addition to tetrasaccharides, 40E and 50E also contained pentasaccharides and hexasaccharides with ß-(1→3)-linked or ß-(1→6)-linked glucose residues. All fractions could inhibit the accumulation of intracellular reactive oxygen species (ROS) in H2O2-induced Caco-2 cells, and they could improve oxidative stress damage by increasing the activity of superoxide dismutase (SOD) and reduced glutathione (GSH), which were related to their DPs and structures. 50E with high DPs showed better anti-oxidative stress activity.

14.
Cell Mol Neurobiol ; 44(1): 50, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856921

ABSTRACT

In recent years, spatial transcriptomics (ST) research has become a popular field of study and has shown great potential in medicine. However, there are few bibliometric analyses in this field. Thus, in this study, we aimed to find and analyze the frontiers and trends of this medical research field based on the available literature. A computerized search was applied to the WoSCC (Web of Science Core Collection) Database for literature published from 2006 to 2023. Complete records of all literature and cited references were extracted and screened. The bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, Bibliometrix R Package software, and Scimago Graphica. A total of 1467 papers and reviews were included. The analysis revealed that the ST publication and citation results have shown a rapid upward trend over the last 3 years. Nature Communications and Nature were the most productive and most co-cited journals, respectively. In the comprehensive global collaborative network, the United States is the country with the most organizations and publications, followed closely by China and the United Kingdom. The author Joakim Lundeberg published the most cited paper, while Patrik L. Ståhl ranked first among co-cited authors. The hot topics in ST are tissue recognition, cancer, heterogeneity, immunotherapy, differentiation, and models. ST technologies have greatly contributed to in-depth research in medical fields such as oncology and neuroscience, opening up new possibilities for the diagnosis and treatment of diseases. Moreover, artificial intelligence and big data drive additional development in ST fields.


Subject(s)
Bibliometrics , Transcriptome , Humans , Transcriptome/genetics , Publications , Animals
15.
J Proteome Res ; 23(7): 2576-2586, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38860290

ABSTRACT

The relationship between antibiotic resistance and bacterial virulence has not yet been fully explored. Here, we use Edwardsiella tarda as the research model to investigate the proteomic change upon oxytetracycline resistance (LTB4-ROTC). Compared to oxytetracycline-sensitive E. tarda (LTB4-S), LTB4-ROTC has 234 differentially expressed proteins, of which the abundance of 84 proteins is downregulated and 15 proteins are enriched to the Type III secretion system, Type VI secretion system, and flagellum pathways. Functional analysis confirms virulent phenotypes, including autoaggregation, biofilm formation, hemolysis, swimming, and swarming, are impaired in LTB4-ROTC. Furthermore, the in vivo bacterial challenge in both tilapia and zebrafish infection models suggests that the virulence of LTB4-ROTC is attenuated. Analysis of immune gene expression shows that LTB4-ROTC induces a stronger immune response in the spleen but a weaker response in the head kidney than that induced by LTB4-S, suggesting it's a potential vaccine candidate. Zebrafish and tilapia were challenged with a sublethal dose of LTB4-ROTC as a live vaccine followed by LTB4-S challenge. The relative percentage of survival of zebrafish is 60% and that of tilapia is 75% after vaccination. Thus, our study suggests that bacteria that acquire antibiotic resistance may attenuate virulence, which can be explored as a potential live vaccine to tackle bacterial infection in aquaculture.


Subject(s)
Drug Resistance, Bacterial , Edwardsiella tarda , Enterobacteriaceae Infections , Oxytetracycline , Tilapia , Zebrafish , Edwardsiella tarda/pathogenicity , Edwardsiella tarda/drug effects , Edwardsiella tarda/genetics , Animals , Oxytetracycline/pharmacology , Virulence/drug effects , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/immunology , Enterobacteriaceae Infections/drug therapy , Tilapia/microbiology , Fish Diseases/microbiology , Fish Diseases/immunology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Proteomics/methods , Bacterial Vaccines/immunology
16.
Life Sci ; 351: 122824, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38862061

ABSTRACT

Inter-organ communication through hormones, cytokines and extracellular vesicles (EVs) has emerged to contribute to the physiological states and pathological processes of the human body. Notably, the liver coordinates multiple tissues and organs to maintain homeostasis and maximize energy utilization, with the underlying mechanisms being unraveled in recent studies. Particularly, liver-derived EVs have been found to play a key role in regulating health and disease. As an endocrine organ, the liver has also been found to perform functions via the secretion of hepatokines. Investigating the multi-organ communication centered on the liver, especially in the manner of EVs and hepatokines, is of great importance to the diagnosis and treatment of liver-related diseases. This review summarizes the crosstalk between the liver and distant organs, including the brain, the bone, the adipose tissue and the intestine in noticeable situations. The discussion of these contents will add to a new dimension of organismal homeostasis and shed light on novel theranostics of pathologies.


Subject(s)
Extracellular Vesicles , Liver Diseases , Liver , Humans , Extracellular Vesicles/metabolism , Extracellular Vesicles/physiology , Liver/metabolism , Animals , Liver Diseases/metabolism , Liver Diseases/pathology , Liver Diseases/physiopathology , Homeostasis/physiology , Adipose Tissue/metabolism , Brain/metabolism , Cytokines/metabolism , Bone and Bones/metabolism
17.
Gut Microbes ; 16(1): 2372881, 2024.
Article in English | MEDLINE | ID: mdl-38940400

ABSTRACT

Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.


Subject(s)
Chemokine CXCL16 , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Liver , Receptors, CXCR6 , Animals , Receptors, CXCR6/metabolism , Chemokine CXCL16/metabolism , Mice , Humans , Liver/metabolism , Liver/microbiology , Lymphocytes/immunology , Lymphocytes/metabolism , Mice, Inbred C57BL , Male , Immunity, Innate , Fatty Liver/therapy , Fatty Liver/metabolism , Fatty Liver/microbiology , Interleukin-22 , Non-alcoholic Fatty Liver Disease/therapy , Non-alcoholic Fatty Liver Disease/microbiology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/immunology , Interleukins/metabolism , Female
18.
Plant Physiol Biochem ; 213: 108806, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38861822

ABSTRACT

The enzyme phospholipase A2 (PLA2) plays a crucial role in acyl remodeling of phospholipids via the Lands' cycle, and consequently alters fatty acid compositions in triacylglycerol (TAG). In this study, a full-length cDNA sequence coding Myrmecia incisa phospholipase A2 (MiPLA2) was cloned using the technique of rapid amplification of cDNA ends. Comparison of the 1082-bp cDNA with its corresponding cloned DNA sequence revealed that MiPLA2 contained 3 introns. Mature MiPLA2 (mMiPLA2) had a conserved Ca2+-binding loop and a catalytic site motif that has been recognized in plant secretory PLA2 (sPLA2) proteins. Correspondingly, phylogenetic analysis illustrated that MiPLA2 was clustered within GroupXIA of plant sPLA2 proteins. To ascertain the function of MiPLA2, the cDNA coding for mMiPLA2 was subcloned into the vector pET-32a to facilitate the production of recombinant mMiPLA2 in Escherichia coli. Recombinant mMiPLA2 was purified and used for the in vitro enzyme reaction. Thin-layer chromatography profiles of the catalytic products generated by recombinant mMiPLA2 indicated a specificity for cleaving sn-2 acyl chains from phospholipids, thereby functionally characterizing MiPLA2. Although recombinant mMiPLA2 displayed a strong preference for phosphatidylethanolamine, it preferentially hydrolyzes arachidonic acid (ArA) at the sn-2 position of phosphatidylcholine. Results from the fused expression of p1300-sp-EGFP-mMiPLA2 illustrated that MiPLA2 was localized in the intercellular space of onion epidermis. Furthermore, the positive correlation between MiPLA2 transcription and free ArA levels were established. Consequently, the role of mMiPLA2 in the biosynthesis of ArA-rich TAG was elucidated. This study helps to understand how M. incisa preferentially uses ArA to synthesize TAG.

19.
Cell Rep Med ; : 101615, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38897205

ABSTRACT

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

20.
Biomed Environ Sci ; 37(4): 367-376, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38727159

ABSTRACT

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.


Subject(s)
Glucosides , Lung Injury , Mice, Inbred C57BL , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Phenols , Sirtuin 1 , Animals , Mice , Glucosides/pharmacology , Glucosides/therapeutic use , Lung/drug effects , Lung/pathology , Lung/metabolism , Lung Injury/drug therapy , Particle Size , Particulate Matter/toxicity , Particulate Matter/adverse effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Sirtuin 1/drug effects , Sirtuin 1/genetics , Sirtuin 1/metabolism
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